The present invention relates to electrochemical sensors for determining gaseous analytes dissolved in an aqueous measuring medium, to a method for the manufacture thereof, and also to a method for determining gaseous analytes dissolved in an aqueous measuring medium using the electrochemical sensors. The invention relates in particular to the reaction space of the electrochemical sensors, which is spatially separated from the aqueous measuring medium by a gas-permeable and ion-impermeable cover layer.
Measuring systems for analysing body fluids are important components of clinically relevant analysis methods. A particular focus of this is rapid and precise measurement of analytes, allowing what are known as point-of-care parameters to be determined. Point-of-care tests have the advantage that the results are available after just a short time, as on the one hand there is no need to transport the samples to a specialist laboratory and on the other hand it is not necessary to take account of the laboratory timescales. Point-of-care tests are carried out mainly in intensive care units and in anaesthesia, but also in outpatient clinics. These “emergency parameters” include the blood gas values (pCO2, pO2), the pH, electrolyte values (for example, Na+, K+, Ca2+, Cl−) and also certain metabolite values.
Test strips or else medical analysers with multiuse sensors can for example be used to carry out point-of-care tests of this type, thus reducing the manual implementation effort to a minimum. Measuring apparatuses for a point-of-care use are generally almost fully automated and require, from the preparation of the samples up to the result of the test, only a small number of simple interventions on the part of the user. They can be embodied both for one-off and for repeated measurement of the parameters to be determined.
Electrochemical sensors have proven particularly suitable for measuring gaseous analytes, such as for example oxygen or carbon dioxide dissolved in whole blood or other aqueous media. Electrochemical sensors allow an analyte to be measured by means of two or more electrodes, at least one of the electrodes being the working electrode at which the analyte to be determined is electrochemically altered (for example, oxidised or reduced).
The measurement of oxygen or the partial pressure (pO2) thereof in an aqueous measuring medium can for example be carried out using amperometric sensors comprising at least one, working electrode and at least one counter electrode. In Clark-type electrodes, a gas-permeable and largely ion and liquid-impermeable membrane generally spatially separates the sample space from the inner electrolyte space. The inner electrolyte space is filled with an electrolyte solution containing a working electrode and a counter electrode.
The measurement of carbon dioxide or the partial pressure (pCO2) thereof in liquids or gases can for example be carried out using potentiometric sensors comprising at least one measuring electrode and at least one reference electrode. In Severinghaus-type electrodes, the measurement of the CO2 partial pressure is reduced to a pH measurement. This generally requires a reaction space which is spatially separated from the aqueous measuring medium by a gas-permeable and largely ion-impermeable membrane. The pH, which is determined by the respective pCO2 value of the sample to be measured, is measured in this reaction space. At a predefined temperature and concentration of the buffer solution in the reaction space (inner electrolyte), the pH of the reaction space is dependent exclusively on the CO2 partial pressure of the sample. The pH can be detected in a broad range of ways, for example potentiometrically via an electrochemical measuring chain using ion-selective glass electrodes or ion-sensitive or ion-selective field effect transistors (ISFETs), pH-sensitive solid-state systems (for example, noble metal/noble metal oxide systems), redox systems (quinhydrone electrode), etc.
An important criterion in the provision of electrochemical sensors is the service life thereof. There is a need to achieve in this regard both a long storage life before the sensor is put into operation and a long in-use service life. In order to ensure a long storage life, the electrodes located in electrochemical sensors should be stored dry, i.e., substantially without water, and not be brought into contact with the liquid inner electrolyte until just before the sensor is put into operation. In order to achieve an in-use service life of at least 500 measurements or 3 to 4 weeks, the various layers of the sensor must also be compatible with one another. It is imperative that they should not become detached from one another or form cracks, for example as a result of swelling.
A further important criterion in the provision of electrochemical sensors for point-of-care tests is the dimensions thereof. Small quantities of samples (for example, 100 μl or less) are generally available in order to determine emergency parameters. If a large number of parameters are to be determined using small quantities of samples, the individual electrodes must be as small as possible and positioned as close together as possible.
EP 0 805 973 B1 discloses a device and also a method for measuring the concentration of gases in a sample. The device used is an electrochemical sensor comprising a working electrode, a counter or reference electrode, an electrolyte layer and a gas-permeable membrane, the electrolyte layer consisting of a photoformed proteinaceous gelatin. In order to avoid premature contamination of the negatively polarised working electrode (cathode), which is made of gold, by positively charged silver ions originating from the counter electrode (anode), which is made of silver, the distance between the two electrodes, which are electrically contacted by a layer of gelatin, must be at least 1 mm.
U.S. Pat. No. 5,387,329 describes a planar electrochemical oxygen sensor in which a swellable polymer, the swell value of which is less than two times its dry volume, is used as a hygroscopic electrolyte and forms in this case a hydrophilic electrolyte layer which is permeable by water and cations. A swellable polymer which is preferred within this document is Nafion®, a sulphonated tetrafluoroethylene polymer, the lithium-charged sulphonate groups of which impart ionomeric properties to the polymer and cause lithium ions to be exchanged for silver ions. In an amperometric oxygen sensor with a silver counter electrode, this reduces the effective speed of migration of the silver ions toward the working electrode.
The electrolyte layers used in EP 0 805 973 B1 and U.S. Pat. No. 5,387,329 have a number of drawbacks. Thus, for example, the production of very thin layers (approx. 1 μm) of swellable polymers (for example the proteinaceous gelatins which are photoformed in EP 0 805 973 B1) is very expensive.
Furthermore, in the case of very thin layers and very low electrolyte volumes, the silver ions released during operation of an oxygen sensor soon lead to interfering signals. On the other hand, if thicker swelling layers (approx. 10-50 μm) are used in a multilayered construction, the formation of leaks in the layer construction is facilitated. This makes it difficult to achieve the desired longevity of the sensor.
In addition, a major drawback of thin, water-containing polymer layers is the fact that, after an electric field is applied between the two electrodes, interfering silver ions migrate on a direct path through the polymer and thus reach and contaminate the working electrode after a relatively short operating period.